New methods developed for the study could be applied to devise personalized, cell-based immunotherapies for epithelial ovarian cancer or other types of tumors
A Ludwig Cancer Research study shows that ovarian cancer, which has proved resistant to currently available immunotherapies, could be susceptible to personalized immunotherapy. Led by Ludwig Lausanne investigator Alexandre Harari and George Coukos, director of the Ludwig Institute for Cancer Research, Lausanne, the study shows that ovarian tumors harbor highly reactive killer T cells—which kill infected and cancerous cells—and demonstrates how they can be identified and selectively grown for use in personalized, cell-based immunotherapies.
“Tumors whose cells tend to be highly mutated, like those of melanoma and lung cancer, are the ones that respond best to immunotherapies,” says Harari. “It has long been a question whether we’d even be able to detect sufficiently mutation-reactive T cells in patients with tumors that have low mutational loads.”
Harari, Coukos and their colleagues report in Nature Communicationsthat, despite their low mutational load, epithelial ovarian tumors are infiltrated with T cells that are especially good at recognizing and killing cancer cells.
Cancer cells that have a relatively large number of mutations in their DNA express aberrant proteins—or neoantigens—that reveal the cancer to the immune system. Killer T cells recognize tiny, mutated bits of these antigens, known as neoepitopes. But neoepitopes vary wildly from patient to patient, even within the same type of cancer. This has long stymied efforts to develop generally effective therapies that target cancer antigens.
To get around this problem, researchers have been developing sophisticated methods to extract T cells from patients, select and expand those that best target a patient’s cancer and reinfuse them into the patient. These approaches usually rely on T cells extracted from the bloodstream, not those already inside the tumor, which are referred to as TILs (for tumor infiltrating lymphocytes).
Experimental therapies using T cells taken from the blood stream have not, however, worked very well against solid tumors. Further, when TILs have been used for such purposes, the proportion of what Harari calls the “juiciest” T cells—those recognizing mutations on cancer cells—tends to decline significantly when the cells are expanded in culture.
“To circumvent these problems, we developed a new methodology to identify highly reactive TILs and expand them in a manner that, rather than diluting the juiciest TILs, enriches them instead,” says Harari. “This allowed us to compare the activity of TILs that target neoepitopes with their counterparts in the peripheral bloodstream.”
The researchers show that killer T cells isolated from ovarian tumors using their method are much better at both recognizing neoepitopes than are those isolated from blood.
“We could even compare T cells from the two compartments targeting the exact same mutation and show that the TILs were more functional than the T cells we collected from the peripheral bloodstream,” says Harari.
Notably, the researchers found that, using their methods, highly reactive TILs could be obtained from some 90% of the ovarian cancer patients whose tumor samples they examined.
“The big message,” says Coukos, “is that future cell-based therapies can be envisioned for low mutational load tumors and should prioritize the use of TILs over T cells collected from peripheral blood. This novel strategy to obtain enriched TILs also offers great therapeutic opportunities.”
Harari, Coukos and their colleagues will now be applying their findings to an ambitious program to develop and streamline personalized immunotherapies for cancer patients currently underway at the Lausanne Branch of the Ludwig Institute for Cancer Research.
The Latest on: Personalized cell-based immunotherapies
via Google News
The Latest on: Personalized cell-based immunotherapies
- Study extends potential for personalized immunotherapy to large variety of cancers on March 15, 2018 at 5:00 pm
The study demonstrates how they can be identified and selectively grown for use in personalized, cell-based immunotherapies. "Tumors whose cells tend to be highly mutated, like those of melanoma and l... […]
- Tmunity Therapeutics Raises $100M in Series A Financing on January 23, 2018 at 9:05 am
The proceeds will be used to advance and expand the business and operational structure of Tmunity to support the rapid translation, development and manufacture of its portfolio of novel T cell based . ... […]
- Medigene highlights a new approach for neoantigen-specific TCRs at Neoantigen Summit 2016 in Boston on November 15, 2016 at 10:30 pm
Medigene concentrates on the development of personalized T cell-based immunotherapies. For more information, please visit www.medigene.com This press release contains forward-looking statements repres... […]
- Scientists Just Made a Major Breakthrough in Personalized Cancer Treatment on March 3, 2016 at 4:00 pm
Scientists at the University College London (UCL) have made a major breakthrough that may further cement ... Juno Therapeutics and Novartis have been working on their own T-cell based immunotherapies ... […]
- RXI Pharma (RXII) Enters Exclusive License Deal with MirImmune for Self-Delivering RNAi (sd-rxRNA) Technology on March 27, 2015 at 6:10 am
RXI Pharma (NASDAQ: RXII) and privately-held MirImmune LLC, today announced that they have entered into an exclusive license agreement to RXi's novel and proprietary sd-rxRNA® technology for use in de... […]
- TxCell's cell therapy facility in Besançon receives GMP compliance certificate from ANSM on June 13, 2014 at 1:07 am
TxCell SA, a biotechnology company developing innovative, personalized cell-based immunotherapies using antigen specific regulatory T-cells (Ag-Tregs) for severe chronic inflammatory and autoimmune di... […]
- Damian Marron appointed as CEO of TxCell on November 7, 2013 at 11:29 pm
TxCell SA, a biotechnology company developing innovative, personalized cell-based immunotherapies, has appointed Damian Marron as chief executive officer (CEO). In addition, Francois Meyer, previously ... […]
- Prima BioMed and Neopharm Ltd Enter Into License for CVac in Israel on November 6, 2013 at 4:13 am
We believe this sends a strong message of confidence in our CVac program and represents Prima's commercial potential to successfully develop cell based immunotherapies for ... active leader in the dev... […]
- Argos Therapeutics Secures $42.5 Million Financing, Funds Pivotal Phase 3 ADAPT Trial for Personalized Immunotherapy on August 27, 2013 at 5:12 am
DURHAM, N.C., Aug. 27, 2013 (GLOBE NEWSWIRE) -- Argos Therapeutics Inc., a biopharmaceutical company focused on the development and commercialization of fully personalized immunotherapies ... on ident... […]
via Bing News